Contribution of the ubiquitin proteasome system to ferroptosis resistance in non-small cell lung cancers (A05)

• Subject Area: Cell Biology ; Hematology, Oncology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

Mutations in the KEAP1 E3 ligase are identified in 30% of patients with NSCLC. These mutations trigger abnormal activation of NRF2, a factor linked to resistance to cell death and therapies. Using a CRISPR screen in KEAP1-mutant and non-mutant cells, we found a relationship between cell death caused by the ferroptosis inducer FIN56 and the CRL5ARIH2/ASB6 ubiquitylation system. Here, we plan to characterize CRL5ARIH2/ASB6 substrates and modulators that contribute to FIN56-induced cell death and to explore their contribution to NSCLC growth. These will reveal the cause of ferroptosis resistance in NSCLC and provide the basis for developing innovative combination strategies to combat this disease.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Head: Professor Dr. José Pedro Friedmann Angeli